一线核苷（酸）类似物经治的慢性乙型肝炎患者低病毒血症的发生及治疗策略

郑嵘炅; 鲁晓擘

doi:10.12449/JCH240506

一线核苷（酸）类似物经治的慢性乙型肝炎患者低病毒血症的发生及治疗策略

DOI: 10.12449/JCH240506

郑嵘炅,
鲁晓擘^, ,

新疆医科大学第一附属医院感染性疾病中心，乌鲁木齐 830054

详细信息

通信作者:
鲁晓擘， xjykdluxiaobo@126.com （ORCID： 0000-0001-5532-7551）

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出版历程
- 收稿日期: 2024-02-29
- 录用日期: 2024-03-30
- 出版日期: 2024-05-25

Low-level viremia in chronic hepatitis B patients treated with first-line treatment with nucleos（t）ide analogues and its treatment strategies

Rongjiong ZHENG,
Xiaobo LU^{,
,}

Center of Infectious Diseases，The First Affiliated Hospital of Xinjiang Medical University，Urumqi 830054，China

More Information

Corresponding author: LU Xiaobo， xjykdluxiaobo@126.com （ORCID： 0000-0001-5532-7551）

摘要

摘要: 强效低耐药口服抗病毒治疗可使HBV复制受到强力抑制，但部分患者接受恩替卡韦、替诺福韦酯、丙酚替诺福韦、艾米替诺福韦治疗48周及以上仍存在低病毒血症（LLV）。国内外多项研究结果提示，抗病毒治疗后LLV与慢性乙型肝炎肝纤维化进展、失代偿期肝硬化和肝细胞癌发生风险以及长期生存率降低密切相关。因此，本文聚焦有关一线核苷（酸）类似物治疗后LLV的发生及其危险因素和临床危害以及不同的治疗方案，以期为今后慢性乙型肝炎患者LLV的治疗提供参考。
- 乙型肝炎，慢性 /
- 核苷类 /
- 核苷酸类 /
- 低病毒血症
Abstract: Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication； however， some patients may still have low-level viremia （LLV） after receiving entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide， or tenofovir amibufenamide for 48 weeks or more. Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis， the risk of decompensated liver cirrhosis and hepatocellular carcinoma， and the reduction in long-term survival rate. Therefore， this article reviews the development， risk factors， and clinical harm of LLV after first-line treatment with nucleos（t）ide analogues， as well as different treatment regimens， in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future.
- Hepatitis B， Chronic /
- Nucleosides /
- Nucleotides /
- Low-Level Viremia

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参考文献(20)

[1]	SHI Y, ZHENG M. Hepatitis B virus persistence and reactivation[J]. BMJ, 2020, 370: m2200. DOI: 10.1136/bmj.m2200.
[2]	YU X, PFEFFERKORN M, van BÖMMEL F, et al. Clinical applications of circulating HBV RNA as a potential surrogate biomarker for intrahepatic cccDNA transcriptional activity[J]. Gut, 2024, 73( 4): 563- 566. DOI: 10.1136/gutjnl-2023-331217.
[3]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(2022 version)[J]. Chin J Infect Dis, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 中华传染病杂志, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050.
[4]	KIM JH, SINN DH, KANG W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology, 2017, 66( 2): 335- 343. DOI: 10.1002/hep.28916.
[5]	TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67( 4): 1560- 1599. DOI: 10.1002/hep.29800.
[6]	LU FM, FENG B, ZHENG SJ, et al. Current status of the research on low-level viremia in chronic hepatitis B patients receiving nucleos(t) ide analogues[J]. J Clin Hepatol, 2021, 37( 6): 1268- 1274. DOI: 10.3969/j.issn.1001-5256.2021.06.007. 鲁凤民, 封波, 郑素军, 等. 核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的研究现状[J]. 临床肝胆病杂志, 2021, 37( 6): 1268- 1274. DOI: 10.3969/j.issn.1001-5256.2021.06.007.
[7]	ZHANG Q, PENG H, LIU XQ, et al. Chronic hepatitis B infection with low level viremia correlates with the progression of the liver disease[J]. J Clin Transl Hepatol, 2021, 9( 6): 850- 859. DOI: 10.14218/JCTH.2021.00046.
[8]	SUN FR, LIU ZF, WANG BY. Correlation between low-level viremia and hepatitis B-related hepatocellular carcinoma and recurrence: A retrospective study[J]. BMC Cancer, 2021, 21( 1): 1103. DOI: 10.1186/s12885-021-08483-3.
[9]	WANG XH, LIU XL, WANG P, et al. Antiviral therapy reduces mortality in hepatocellular carcinoma patients with low-level hepatitis B viremia[J]. J Hepatocell Carcinoma, 2021, 8: 1253- 1267. DOI: 10.2147/JHC.S330301.
[10]	SUN YM, WU XN, ZHOU JL, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18( 11): 2582- 2591. e 6. DOI: 10.1016/j.cgh.2020.03.001.
[11]	CHEN H, FU JJ, LI L, et al. Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: A retrospective cohort study[J]. J Gastroenterol Hepatol, 2024, 39( 1): 180- 184. DOI: 10.1111/jgh.16357.
[12]	WANG LJ, GU ZQ, XU ZM, et al. A possible mechanism for low-level viremia occurrence in nucleos(t)ide analog-treated chronic hepatitis B patients[J]. Chin J Hepatol, 2021, 29( 12): 1151- 1155. DOI: 10.3760/cma.j.cn501113-20211124-00578. 王雷婕, 顾智强, 许梓萌, 等. 核苷(酸)类药物经治慢性乙型肝炎患者低病毒血症发生的可能机制[J]. 中华肝脏病杂志, 2021, 29( 12): 1151- 1155. DOI: 10.3760/cma.j.cn501113-20211124-00578.
[13]	LI J, DONG XQ, CAO LH, et al. Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment[J]. Front Cell Infect Microbiol, 2023, 13: 1151899. DOI: 10.3389/fcimb.2023.1151899.
[14]	LU JH, ZHANG CN, HE PY, et al. Risk factors for very low-level viremia in patients with chronic hepatitis B virus infection: A single-center retrospective study[J]. Liver Res, 2022, 6( 1): 39- 44. DOI: 10.1016/j.livres.2022.02.001.
[15]	WANG YS, KONG Y, LIU YY, et al. Different switching therapy for chronic hepatitis B patients with low-level viraemia: A single-center retrospective study[J]. J Pract Hepatol, 2022, 25( 5): 633- 636. DOI: 10.3969/j.issn.1672-5069.2022.05.007. 王玉珊, 孔银, 刘元元, 等. 不同转换治疗策略对经治的低病毒血症慢性乙型肝炎患者疗效的影响: 单中心回顾性研究[J]. 实用肝脏病杂志, 2022, 25( 5): 633- 636. DOI: 10.3969/j.issn.1672-5069.2022.05.007.
[16]	European Association for the Study of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67( 2): 370- 398. DOI: 10.1016/j.jhep.2017.03.021.
[17]	ISHIDO S, TAMAKI N, UCHIHARA N, et al. Switching from entecavir to tenofovir alafenamide for maintaining complete virological response in chronic hepatitis B[J]. JGH Open, 2023, 7( 8): 567- 571. DOI: 10.1002/jgh3.12950.
[18]	LI ZB, LI L, NIU XX, et al. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia[J]. Liver Int, 2021, 41( 6): 1254- 1264. DOI: 10.1111/liv.14786.
[19]	WANG YH, LIAO J, ZHANG DM, et al. Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir[J]. J Med Virol, 2020, 92( 3): 302- 308. DOI: 10.1002/jmv.25608.
[20]	LIU LP, WU XP, CAI TP, et al. Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia[J]. Chin J Hepatol, 2023, 31( 2): 118- 125. DOI: 10.3760/cma.j.cn501113-20221019-00507. 刘丽萍, 邬小萍, 蔡天盼, 等. 恩替卡韦经治后低病毒血症的慢性乙型肝炎患者序贯联合富马酸丙酚替诺福韦治疗的疗效及影响因素分析[J]. 中华肝脏病杂志, 2023, 31( 2): 118- 125. DOI: 10.3760/cma.j.cn501113-20221019-00507.